Anti-cancer agents in medicinal chemistry最新文献

{"title":"Advancements in Metal Complexation of Pyridine Derivatives (2022-2024): A Pathway to Enhanced Anticancer Potency.","authors":"Nouf A Babteen","doi":"10.2174/0118715206378693250414044912","DOIUrl":"https://doi.org/10.2174/0118715206378693250414044912","url":null,"abstract":"<p><p>Cancer remains a major global health challenge, necessitating innovative therapies that selectively target cancer cells while sparing healthy tissues. Pyridine and its derivatives have gained prominence in medicinal chemistry for their structural diversity and biological activity. However, their therapeutic potential is often hindered by low bioavailability, poor solubility, and rapid metabolism. Metal complexation has emerged as a promising solution, with pyridine nitrogen serving as an excellent coordination site for transition metals. These pyridinemetal complexes enhance stability, bioavailability, and anticancer properties, exhibiting potent cytotoxicity through mechanisms like ROS generation, DNA intercalation, and apoptosis induction. This review highlights the latest progress (2022-2024) in the field, emphasizing the structural modifications, and mechanistic insights that have propelled pyridine-metal complexes as potent anticancer agents. Special attention is given to the role of metal complexation in enhancing the anticancer potency of pyridine derivatives, with examples of preclinical studies showing their efficacy against various cancer types. The findings emphasize the potential of pyridine-metal complexes as a transformative approach in oncology, bridging the gap between innovative chemical design and impactful therapeutic applications.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methyl (Z)-2-(Isothioureidomethyl)-2-pentenoate Hydrobromide Induces Cell Cycle Arrest and Disrupts Mitosis in a Melanoma Cell Line.","authors":"Laura Sartori Assunção, Iara Patricia Kretzer, Jelver Alexander Sierra Restrepo, Leonidas João de Mello Junior, Flavio Augusto Rocha Barbosa, Misael Ferreira, Marcus Mandolesi Sá, Tânia Beatriz Creczynski-Pasa","doi":"10.2174/0118715206358941250413154017","DOIUrl":"https://doi.org/10.2174/0118715206358941250413154017","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Cancer is a global health burden. Despite advances in early detection and therapeutics, cancer prevalence continues to increase, underscoring the need for innovative therapeutic strategies. Dysregulation of cell death mechanisms is a hallmark of cancer that can lead to apoptosis evasion, which strongly contributes to tumor progression and therapy resistance. Isothiouronium salts have attracted attention as promising antitumor agents. This study aimed to evaluate the in vitro antitumor effect of an isothiouronium salt (ISMF08) on the B16F10 melanoma cell line.</p><p><strong>Methods: </strong>The antitumor properties of IS-MF08 were investigated by incubating B16F10 cells with the compound at different concentrations. Cytotoxicity was determined by the (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) (MTT) assay, cell cycle arrest and cell death mechanisms by flow cytometry, and morphological alterations by transmission electron microscopy. Physicochemical parameters related to druglikeness were predicted in silico using the SwissADME tool.</p><p><strong>Results: </strong>IS-MF08 was cytotoxic to melanoma cells, triggering cell cycle arrest and disrupting mitosis. The mechanism of cell death was compatible with apoptosis, as indicated by annexin V-FITC experiments and the relevant morphological changes in cell structure observed by transmission electron microscopy. SwissADME predicted that IS-MF08 has good physicochemical properties related to absorption and permeation.</p><p><strong>Conclusion: </strong>The numerous mechanisms of cell death triggered by IS-MF08 and its drug-likeness make it an interesting molecule in the search for new antitumor compounds, contributing to therapies targeting the dysregulation of cellular mechanisms such as apoptosis.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Benzothiazole-Based 1,3,4-Thiadiazole Derivatives as Potential Anticancer Agents.","authors":"Beyza Ecem Öz Bedir, Emine Terzi, Tuba Ozdemir Sanci, Francesco Melfi, Ecem Kaya-Sezginer, Betül Kaya, Ulviye Acar Çevik","doi":"10.2174/0118715206353584241018051852","DOIUrl":"https://doi.org/10.2174/0118715206353584241018051852","url":null,"abstract":"<p><strong>Objective: </strong>The present study aimed to design and synthesize a new series of benzothiazole analogues containing 1,3,4-thiadiazole, and assess their biological activities as potential anticancer agents.</p><p><strong>Methods: </strong>N-(5,6-dimethylbenzo[d]thiazol-2-yl)-2-((5-(substituted amino)-1,3,4-thiadiazol-2-yl)thio)acetamide derivatives (4a-4h) were synthesized via the reaction of thiadiazole derivatives (3a-3h) with 2-chloro-N-(5,6- dimethylbenzo[d]thiazol-2-yl)acetamide (1) in the presence of potassium carbonate. All the target compounds have been characterized by spectral analysis. The anticancer activities of compounds 4a-4h were tested against two human HT-1376 bladder and HT-29 colorectal carcinoma cells using the WST-1 assay. Flow cytometry was used for the determination of apoptosis, cell cycle, and caspase 3/7 activity. Moreover, wound-healing assay was utilized to evaluate cell migration. In silico physicochemical, pharmacokinetics, and toxicological properties of compound 4g were determined by pkCSM, SwissADME, and SwissTargetPrediction online web tools.</p><p><strong>Results: </strong>Among all synthesized derivatives, compound 4g (N-(5,6-dimethylbenzo[d]thiazol-2-yl)-2-((5-((3- methoxyphenyl)amino)-1,3,4-thiadiazol-2-yl)thio)acetamide) recorded the highest antiproliferative activity against HT-1376 cells with an IC50 as 26.51 μM at 24 h, which was less cytotoxic than cisplatin (IC50=14.85 μM). The combined treatment with compound 4g and cisplatin increased the cellular apoptosis with a higher impact compared with the cisplatin group. The higher accumulation of cells in the G2 phase, a significant increase of caspase 3/7 activity, and the inhibition of migration rate were also observed in HT-1376 following a combination of compound 4g and cisplatin treatment versus cisplatin alone, which might be involved in the apoptotic effects of compound 4g.</p><p><strong>Conclusion: </strong>The in vitro anticancer potential of compound 4g lays the foundation for future research to focus on its value as a novel and advanced cancer therapy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Approaches on Oncolytic Viruses, Aptamers, TTFields and Personalized Treatment used for the Management of Glioblastoma: A Comprehensive Review.","authors":"Archna Singh, Anmol Kanda, Jyoti Kanda","doi":"10.2174/0118715206364677250401190214","DOIUrl":"https://doi.org/10.2174/0118715206364677250401190214","url":null,"abstract":"<p><p>Glioblastoma (GB) remains a formidable challenge in oncology, with current treatment approaches providing only marginal improvements in patient outcomes. Despite significant advances in understanding its molecular and genetic characteristics, median survival for untreated patients remains distressingly low, emphasizing the urgent need for novel therapeutic strategies. This review comprehensively examines the standard first-line treatments for GB, including surgery, concomitant radio-chemotherapy, and maintenance chemotherapy, while highlighting the limitations of these approaches. Consequently, we explore emerging novel therapeutic modalities such as Oncolytic Viral Therapy with genetically modified oncolytic viruses that enhance the capabilities of antigen- presenting cells. These cells migrate to lymph nodes to recruit cytotoxic CD8+ T lymphocytes, directing them to the site of infection where they eradicate cells that promote tumour growth. Aptamer-based therapies, such as GMT-3, AS1411, GS24, GMT8, and Gint4.T, which exhibit specificity for their biological targets and can act as drug transporters by facilitating receptor-mediated transcytosis within the endothelial cells of the blood-brain barrier, thus improving drug delivery. Tumour-treating fields (TTFields) that have shown increased overall survival rates in patients. Personalized genomic medicine, driven by biomarkers, which provokes immune responses tailored to the tumour's specific antigens, thereby customizing patient-specific treatments to improve effectiveness. By synthesizing current evidence and recent breakthroughs, we underscore the potential use of advancing novel therapies to address the unmet clinical needs of GB patients and ultimately enhance their overall survival and quality of life.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Characteristics and Prognostic Factors Associated with Herpes Zoster in Patients with Malignant Tumors: A Systematic Review and Meta-analysis.","authors":"Mingming Ding, Shantao Qiu, Guan Jiang","doi":"10.2174/0118715206350399250324183333","DOIUrl":"https://doi.org/10.2174/0118715206350399250324183333","url":null,"abstract":"<p><strong>Background: </strong>Herpes zoster (HZ) is a common complication in patients with malignant tumors (MT), impacting prognosis. Immunocompromised states due to malignancy or treatment increase HZ risk. However, comprehensive assessments of HZ's clinical features and its impact on prognosis in these patients are limited, general conclusions are challenging, prompting a systematic review and meta-analysis to better understand the relative risk of HZ in malignancy.</p><p><strong>Objective: </strong>To assess the clinical features and prognostic factors of HZ in cancer patients through systematic review and meta-analysis. The study aimed to calculate the relative risk of HZ in malignancy and analyze factors affecting prognosis, such as age, gender, tumor type, and treatment.</p><p><strong>Methods: </strong>A systematic search in PubMed (2016-2024) identified studies on HZ and malignancy. Two reviewers independently screened and selected studies, extracting data on study characteristics, population demographics, and outcomes. Statistical heterogeneity across the studies was addressed using random-effects models, while subgroup analyses were performed to identify potential sources of heterogeneity.</p><p><strong>Results: </strong>Out of the 633 records reviewed, 13 studies satisfied the eligibility criteria and were incorporated into the meta-analysis. The combined relative risk for any type of cancer was found to be 1.82(95% CI: 1.29,2.57). The combined relative risk for any solid tumors was 1.63(95% CI: 1.08,2.46). The combined relative risk for any haematological cancer was 3.43(95% CI: 1.33,8.86). The combined analysis of all treatment modalities (including Radiotherapy, Chemotherapy, Immunosuppression, HSCT) shows a significant overall effect with a risk ratio of 1.78(95%CI: 1.59,2.00).</p><p><strong>Conclusion: </strong>Cancer patients have increased HZ risk due to immunosuppression from the malignancy and its treatment, especially in hematological cancers and those undergoing stem cell transplantation.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Therapeutic Potential of Dual-Acting Aromatase/COX-2.","authors":"Ali Aliabadi, Mobina Tajdari, Sara Fakharinia, Niusha Sadat Ashrafizadeh, Maryam Bayanati, Mohammad Mahboubi-Rabbani, Afshin Zarghi","doi":"10.2174/0118715206359499250318063747","DOIUrl":"https://doi.org/10.2174/0118715206359499250318063747","url":null,"abstract":"<p><p>Aromatase, a crucial enzyme assigned for transforming androgen into estrogen, has a vital function in the advancement of drug-resistant breast cancers that respond to endocrine treatments. Aromatase (CYP19A1) is a monooxygenase from the cytochrome P450 family that is involved in the conversion of androgens to estrogens. Breast cancer cells express aromatase activity, indicating that the tumor cells may be able to produce local estrogen. By inhibiting aromatase, serum estrogen levels decrease, which, in turn, hinders estrogen-driven cancer cell growth in hormone receptor-positive breast cancer cases. In this sense, the introduction of novel aromatase inhibitors could be a significant step forward in the fight against cancer. This is especially true in hormone-dependent cancers. Many compounds have been introduced as aromatase inhibitors, classified as steroidal or nonsteroidal. However, it should be noted that these drugs have encountered resistance in numerous cases, particularly in recent years. Thus, the search for new aromatase inhibitor drugs has always been critical. Newly, there seems to be a surge of enthusiasm in the discovery and production of molecules with dual inhibitory effects, which can inhibit two or more enzymes simultaneously. This method enables a significant reduction in potential drug resistance. The design of these compounds has an opportunity to significantly boost the efficacy of anti-cancer treatments by causing synergistic effects. This article offers a review of newly developed aromatase inhibitors with potential anticancer effects.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Role of Tumor-infiltrating Immune Cells in Modulating Cancer Drug Resistance.","authors":"Shima Mehrabadi","doi":"10.2174/0118715206365310250310081445","DOIUrl":"https://doi.org/10.2174/0118715206365310250310081445","url":null,"abstract":"<p><p>Tumor-infiltrating immune cells (TIICs) have been identified as critical components in the development of cancer drug resistance. This review aims to discuss the various types of TIICs, such as macrophages and T cells, that have been linked to cancer drug resistance. Furthermore, we explore the mechanisms by which TIICs contribute to drug resistance and how these mechanisms may differ across various tumor types. Additionally, we examine the potential of immune checkpoint inhibitors in combination with traditional cancer therapies as a strategy to overcome TIIC-mediated cancer drug resistance. In conclusion, this review provides an in-depth analysis of the current knowledge on the role of TIICs in cancer drug resistance and highlights potential avenues for future research to develop more effective treatment strategies. The findings presented in this review emphasize the importance of understanding the complex interactions between cancer cells and the immune system in order to develop novel therapeutic approaches that can overcome TIIC-mediated cancer drug resistance.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Evaluation of Optical Properties, SHP2 Inhibitory Activity, and Cellular Imaging for Novel 2-Quinolone Derivatives.","authors":"Chun Zhang, Yuting Yang, Li-Xin Gao, Suya Gan, Jia Li, Xin Wang, Yu-Bo Zhou, Wen-Long Wang","doi":"10.2174/0118715206337347250219112715","DOIUrl":"https://doi.org/10.2174/0118715206337347250219112715","url":null,"abstract":"<p><strong>Introduction: </strong>Although the development of SHP2 inhibitors has made striking progress, there is no inhibitor in clinical evaluation because of the potential side effects induced by poor drug distribution. Fluorescence imaging technology is widely used in the process of diagnosis and treatment of diseases because of the advantages of rapid imaging and non-destructive detection and might provide a new way to explore the mechanism of drug-target interactions in intact tissue.</p><p><strong>Method: </strong>A series of 2-quinolone derivatives as fluorescent inhibitors against SHP2 were designed and synthesized, and their spectral properties and biological activities were evaluated in this report. The representative compound 8A had excellent fluorescence properties (λ : 562 nm, Stokes shift: 170 nm, fluorescence quantum yield: 0.072) and optical stability.</p><p><strong>Results: </strong>Moreover, compound 8A emitted a blue signal in SHP2WT U2OS cells and inhibited the SHP2 enzyme abilities (IC50: 20.16 ± 0.95 μM) without the extra combination of suitable fluorophores, linker, or selectiveactivated molecules.</p><p><strong>Conclusion: </strong>Therefore, we hope that compound 8A could act as a lead to develop novel, convenient, and bifunctional chemical tools to explore the mechanism of drug-target interactions in intact tissue and promote the integrated research progress of diagnosis and treatment of SHP2 related diseases.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress on Small Molecule Inhibitors of MDM2-p53 Protein-protein Interaction.","authors":"Meiyao Hu, Chang Xu, Mingxin Xu, Siyu He, Dandan Liu","doi":"10.2174/0118715206358340250121060830","DOIUrl":"https://doi.org/10.2174/0118715206358340250121060830","url":null,"abstract":"<p><p>The p53 protein, renowned as the \"anti-cancer protein,\" plays a critical role in regulating the cell cycle, inducing apoptosis, and repairing DNA. Its dysregulation often leads to genomic instability and tumorigenesis. MDM2, a key negative feedback regulator of p53, inhibits both the transcriptional activity and stability of p53, thereby suppressing the anti-cancer effect of p53. With the resolution of the co-crystal structure of the MDM2- p53 complex, using small molecule inhibitors to block their interaction has emerged as a promising cancer treatment strategy. These inhibitors can remove the negative regulation of MDM2 on p53 and allow p53 to function as a \"tumor suppressor protein\". Over recent decades, researchers have designed and synthesized small-molecule inhibitors with diverse structures, showing notable anti-cancer efficacy in preclinical studies. Although several inhibitors have entered clinical trials, none have yet been approved. This review comprehensively summarizes the recent advancements in small-molecule inhibitors of MDM2-p53 protein-protein interaction (PPI) according to different types of structural scaffolds, primarily focusing on imidazolines, spirooxindoles, pyrrolidines, pyrrolones, piperidines, piperidines, purine carboxylic acid derivatives, isoquinolines, pyrazolopyrolidinone analogs, imidazothiazoles, quinolones, and spiroindolines. Additionally, this review focuses on their design, synthesis, and biological evaluation and highlights the structure-activity relationships and ongoing efforts. Despite the progress made, challenges remain. Researchers are exploring strategies to overcome these obstacles in promoting the research on drugs targeting MDM2-p53 PPI with stronger affinity, higher permeability, and a more significant effect.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary Investigations on Acyl Hydrazones Bearing Sulfonamides as Inhibitors of the Human Carbonic Anhydrase Isoforms I, II, IX, and XII.","authors":"Efe Doğukan Dincel, Ebru Didem Kuran, Abdulilah Ece, Faika Başoğlu-Ünal, Gioele Renzi, Gloria Badii, Fabrizio Carta, Cladiu T Supuran, Nuray Ulusoy-Güzeldemirci","doi":"10.2174/0118715206356980250113074705","DOIUrl":"10.2174/0118715206356980250113074705","url":null,"abstract":"<p><strong>Aim: </strong>The present study aims to identify the synthesis and structural characterization of acyl hydrazone- sulfonamide-containing compounds that were tested in vitro on human carbonic anhydrase (hCA) isoforms I, II, IX, and XII.</p><p><strong>Methods: </strong>Herein, acyl hydrazone derivatives containing the primary sulfonamide moiety were synthesized via a three-step synthetic pathway starting from the commercially available 4-sulfamoyl benzoic acid. Structural characterizations of the final compounds were assessed through IR IR, 1H-NMR, 13C-NMR, and elemental analyses. The in vitro profiling activity of the final compounds on the Carbonic Anhydrases (CAs; EC 4.2.1.1) I, II, IX, and XII were performed by means of the stopped-flow technique and revealed nanomolar inhibitory potencies on the selected targets. Molecular docking and molecular dynamic simulations afforded a detailed understanding of the binding modes of the most effective compounds.</p><p><strong>Results: </strong>We reported the synthesis and structural characterization of 25 acyl hydrazone-sulfonamide-containing compounds that were tested in vitro on the hCAs I, II, IX, and XII isoforms for their inhibitory features. Overall, all compounds showed nanomolar inhibition potencies on the panel of hCAs considered, and their binding modes were deciphered by means of in-silico studies. Molecular docking followed by MD simulations confirmed the stability of 4l-hCA I, 4n-hCA II, 4t-hCA II, 4v-hCA XII, and 4w-hCA XII complexes.</p><p><strong>Conclusion: </strong>This study presents a deep understanding of the structural determinants influencing the affinity and selectivity of the designed compounds towards different hCAs, thus offering valuable insights for further optimization and development in the field.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}